[HTML][HTML] A consensus molecular classification of muscle-invasive bladder cancer
European urology, 2020•Elsevier
Background Muscle-invasive bladder cancer (MIBC) is a molecularly diverse disease with
heterogeneous clinical outcomes. Several molecular classifications have been proposed,
but the diversity of their subtype sets impedes their clinical application. Objective To achieve
an international consensus on MIBC molecular subtypes that reconciles the published
classification schemes. Design, setting, and participants We used 1750 MIBC transcriptomic
profiles from 16 published datasets and two additional cohorts. Outcome measurements and …
heterogeneous clinical outcomes. Several molecular classifications have been proposed,
but the diversity of their subtype sets impedes their clinical application. Objective To achieve
an international consensus on MIBC molecular subtypes that reconciles the published
classification schemes. Design, setting, and participants We used 1750 MIBC transcriptomic
profiles from 16 published datasets and two additional cohorts. Outcome measurements and …
Background
Muscle-invasive bladder cancer (MIBC) is a molecularly diverse disease with heterogeneous clinical outcomes. Several molecular classifications have been proposed, but the diversity of their subtype sets impedes their clinical application.
Objective
To achieve an international consensus on MIBC molecular subtypes that reconciles the published classification schemes.
Design, setting, and participants
We used 1750 MIBC transcriptomic profiles from 16 published datasets and two additional cohorts.
Outcome measurements and statistical analysis
We performed a network-based analysis of six independent MIBC classification systems to identify a consensus set of molecular classes. Association with survival was assessed using multivariable Cox models.
Results and limitations
We report the results of an international effort to reach a consensus on MIBC molecular subtypes. We identified a consensus set of six molecular classes: luminal papillary (24%), luminal nonspecified (8%), luminal unstable (15%), stroma-rich (15%), basal/squamous (35%), and neuroendocrine-like (3%). These consensus classes differ regarding underlying oncogenic mechanisms, infiltration by immune and stromal cells, and histological and clinical characteristics, including outcomes. We provide a single-sample classifier that assigns a consensus class label to a tumor sample’s transcriptome. Limitations of the work are retrospective clinical data collection and a lack of complete information regarding patient treatment.
Conclusions
This consensus system offers a robust framework that will enable testing and validation of predictive biomarkers in future prospective clinical trials.
Patient summary
Bladder cancers are heterogeneous at the molecular level, and scientists have proposed several classifications into sets of molecular classes. While these classifications may be useful to stratify patients for prognosis or response to treatment, a consensus classification would facilitate the clinical use of molecular classes. Conducted by multidisciplinary expert teams in the field, this study proposes such a consensus and provides a tool for applying the consensus classification in the clinical setting.
Elsevier
